Amendment made to clarify eligibility, refine outcome measurements, and expand the scope of the study's safety and funding considerations. Administrative Changes: Protocol title updated from version 5.0 (Feb 2016) to version 6.0 (June 2017). Expanded sponsor list, adding the National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Child Health and Human Development (NICHD), and American Diabetes Association (ADA). Inclusion/Exclusion Criteria: Weight eligibility changed from ≥20 kg to ≥16 kg. Pregnancy exclusion criteria adjusted from "within 3 months" to "14 weeks" post-treatment for consistency. Primary Outcome Clarification: OGTT timing for diagnosing abnormal glucose tolerance (AGT) or diabetes updated. AGT or diabetes onset is now defined by the date of the confirmatory abnormal OGTT. Side Effects: Common: Infusion-related reactions (e.g., nausea, dizziness), respiratory and urinary infections. Uncommon: Immune system effects, such as increased risk of infections, low white blood cell counts, changes in heart rate, gastrointestinal irritation, and mood changes. Rare: Severe allergic reactions, possible increased infection risk, and potential long-term risks like cancer (though not observed in previous studies). Funding Sources: Updated to reflect expanded financial support, including the NIAID, NIDDK, and NICHD. Bristol-Myers Squibb continues to provide the abatacept medication.

Amendment to focus on extending follow-up procedures, refining study power estimates, closing enrollment, and outlining interim analysis protocols to assess effectiveness and safety. Follow-up Studies: Subjects with confirmed abnormal glucose tolerance (AGT) will continue to be monitored for diabetes development and safety, even after the study concludes. Non-diabetic subjects will either be monitored through the TN01 study or offered follow-up in the TrialNet LIFT Study if diagnosed with diabetes. Study Power and Enrollment: The study is designed to have 80% power to detect a 40% risk reduction in AGT over six years. A total of 206 participants will be enrolled in a 1:1 ratio between groups. Enrollment closed on July 31, 2019, with follow-up continuing for two more years. Adjusted estimates suggest 64-70 AGT events will occur by study end, enabling hazard ratios between 0.496 to 0.512. Interim Monitoring Plan: Interim analyses will be conducted at equal intervals and reviewed by the Data and Safety Monitoring Board (DSMB). The first interim analysis is planned after 50% of events are observed. The trial could be prematurely terminated if significant effects are detected.